Summary of the Workshop on Issues in Risk Assessment: Quantitative Methods for Developmental Toxicology

This report summarizes the proceedings of a conference on quantitative methods for assessing the risks of developmental toxicants. The conference was planned by a subcommittee of the National Research Council's Committee on Risk Assessment Methodology ⁴ in conjunction with staff from several federal agencies, including the U.S. Environmental Protection Agency, U.S. Food and Drug Administration, U.S. Consumer Products Safety Commission, and Health and Welfare Canada. Issues discussed at the workshop included computerized techniques for hazard identification, use of human and animal data for defining risks in a clinical setting, relationships between end points in developmental toxicity testing, reference dose calculations for developmental toxicology, analysis of quantitative dose-response data, mechanisms of developmental toxicity, physiologically based pharmacokinetic models, and structure-activity relationships. Although a formal consensus was not sought, many participants favored the evolution of quantitative techniques for developmental toxicology risk assessment, including the replacement of lowest observed adverse effect levels (LOAELs) and no observed adverse effect levels (NOAELs) with the benchmark dose methodology.     

Significance of the Dermal Route of Exposure to Risk Assessment

The skin is a route of exposure that needs to be considered when conducting a risk assessment. It is necessary to identify the potential for dermal penetration by a chemical as well as to determine the overall importance of the dermal route of exposure as compared with inhalation or oral routes of exposure. The physical state of the chemical, vapor or liquid, the concentration, neat or dilute, and the vehicle, lipid or aqueous, is also important. Dermal risk is related to the product of the amounts of penetration and toxicity. Toxicity involves local effects on the skin itself and the potential for systemic effects. Dermal penetration is described in large part by the permeability constant. When permeability constants are not known, partition coefficients can be used to estimate a chemical's potential to permeate the skin. With these concepts in mind, a tiered approach is proposed for dermal risk assessment. A key first step is the determination of a skin-to-air or skin-to-medium partition coefficient to estimate a potential for dermal absorption. Building a physiologically-based pharmacokinetic (PBPK) model is another step in the tiered approach and is useful prior to classical in vivo toxicity tests. A PBPK model can be used to determine a permeability constant for a chemical as well as to show the distribution of the chemical systemically. A detailed understanding of species differences in the structure and function of the skin and how they relate to differences in penetration rates is necessary in order to extrapolate animal data from PBPK models to the human. A study is in progress to examine anatomical differences for four species.     

DO DRINKERS KNOW WHEN TO SAY WHEN? AN EMPIRICAL ANALYSIS OF DRUNK DRIVING

This paper presents empirical evidence that an individual's decision to drive while drunk is negatively affected by the expected full price of driving drunk. The analysis uses a unique data set containing information on self-reported drunk driving matched to state-level drunk driving policies as well as to state excise taxes on beer. These are hypothesized and found to affect drunk driving. Further, we find interesting racial differences but surprisingly small differences by gender in the effect of socioeconomic and policy variables on drunk driving propensities.     

The nature of gender

I explain a biosocial model of women’s gendered behavior (behavior on which the sexes differ). This model integrates a macro sociological theory with a biological theory derived from primate behavior. The sociological model is designed to explain changes in the relationship between sex and behavior over time or between groups. The biological model is designed to explain individual within-sex variance and between-sex variance in gendered behavior in a cohort. Results from an original study are presented to demonstrate that within-sex variance in women’s gendered behavior is explained well by the primate model. I conclude that human nature is gendered. The implications of this conclusion are explored for demographic and other social science research.     

One parent or two? The intertwining of American marriage and fertility patterns

Marriage and fertility in the United States have become less firmly entwined as more women bear children without marrying and more couples with children divorce. Today a sizeable number of children are expected to spend a portion of their childhood in one-parent households. Despite the trends in illegitimacy and divorce, the actual effect of out-of-wedlock childbearing on the living arrangements of children has not been fully explicated. Using the National Survey of Family Growth Cycle III, this paper estimates the probability that children aged 0–13 in 1982 are living in two-parent households, controlling for their mothers' marital statuses at their births. We find that marital status at birth is an important predictor of household structure at later ages for both white and black populations; however, the childhood environment is actually quite elastic as women marry, divorce, remarry, and redivorce.     

The Meaning of Work and Love: Career Issues and Interventions

Examining concepts about work and love can help people increase their career success and life satisfaction. Career counselors may initiate this examination by eliciting clients' concepts about work and love. After hearing a client's ideas about work and love, counselors can compare this personal meaning to the social meaning of work and love. When this comparison reveals dysfunctional beliefs about work and love, counselors can link these beliefs to their client's career concerns. Such a linkage typically provokes a cognitive dissonance that motivates clients to modify their beliefs. Counselors can facilitate meaning modification by using client-centered and social influence techniques.     

EVALUATING CHANGES IN THE DISTRIBUTION OF CAPITAL WEALTH

A small-scale general equilibrium model in which the distribution of capital wealth is a key parameter is employed to examine the potential economic consequences of greater capital wealth equality. Every performance indicator examined – aggregate income, consumption equality, social welfare in the sum-of-utilities sense, and aggregate saving –is improved by greater capital wealth equality. However, the bottom-line social welfare gain, relative to the present high-inequality situation – even from the maximum achievable level of complete equality in capital wealth distribution – would be numerically rather modest.     

RURAL POVERTY, URBAN POVERTY, AND PSYCHOLOGICAL WELL-BEING

Data from the National Survey of Families and Households are used to compare the psychological well-being of the rural and urban poor. Overall, the urban poor are higher in perceived health than the rural poor, although no differences are apparent in happiness or depression. Significant interactions are present between rural/urban poverty and sex, race, and family status. The psychological well-being of poor African Americans is higher in rural than urban areas, whereas the well-being of poor whites is higher in urban than rural areas. This trend is especially pronounced for depression among males. In addition, single men without children have especially high depression scores in rural areas, whereas married women without children have especially low depression scores in urban areas. The results are interpreted in terms of the environmental quality of inner-city neighborhoods and attitudes toward poverty in urban and rural communities.     

Cognitive and behavioral therapies for pathological gambling

The purpose of this paper is to provide an overview of behavioral and cognitive treatment approaches in the management of pathological gambling disorders. Disappointingly, the literature to date contains only one controlled outcome study in which two differing behavioral techniques were compared. Although research in general has focussed on identifying the nature of cognitive distortions in gambling, findings from these studies have not been systematically translated into treatment programs. It is concluded that methodological limitations including small sample size, absence of control groups, multiple concurrent interventions and poorly defined outcome criteria preclude conclusive statements to be drawn regarding the active ingredient of either behavioral or cognitive strategies. The program offered within the Impulse Disorders Research Centre is outlined.The authors wish to gratefully acknowledge the assistance and contribution of Zachary Steel, Research Assistant, in the preparation of this paper.